This Small Business Innovation Research Phase I project will develop and demonstrate a prototype Hypoxia Perfusion Bioreactor (HPB). In order to utilize recent discoveries that low oxygen levels are favorable to stem cell expansion, Resodyn Corporation has developed the HPB, which is designed to provide controlled delivery of both oxygen and fresh medium to stem cell cultures. Studying and controlling the physical parameters are essential in order to bring reproducible, economically feasible therapies to the clinic. One goal of this Phase II proposal is to evaluate and demonstrate the utility and commercial feasibility of Resodyn Corporation's Hypoxia Perfusion Bioreactor (HPB) for wide range of hematopoietic cell expansion applications. A second goal is to develop a model protocol that will demonstrate the HPB's ability to expand hematopoietic stem cells (HSCs) without the requirement for previous selection (CD34+ or AC133+) for primitive stem cell populations. This capability would represent a significant advance in reducing the cost and complexity of therapeutic and research efforts in the stem cell field. While the primary feasibility of the HPB will be tested primarily with hematopoietic cell populations, the benefits of this device (controlled hypoxia/oxygen levels, high cell densities, reduced labor, lower contamination risk) would have extended utility to other types of stem and progenitor cells (mesenchymal, adipose, neural, etc.), as well as for use in general mammalian cell culture. Such applications include hybridoma culture for monoclonal antibody (MAb) production and Chinese Hamster Ovary (CHO) cell culture for production of recombinant proteins. The HPB system has significant long-term commercial potential both in the laboratory as a tool to facilitate development of stem cells protocols, and in the clinic as a component of both hematopoietic transplantation and other pre-emerging stem cell therapies of the neural, hematopoietic, and mesenchymal lineages. PUBLIC HEALTH RELEVANCE: This Small Business Innovation Research Phase I project will develop and demonstrate a Hypoxia Perfusion Bioreactor (HPB). The HPB is a single-use bioreactor designed specifically for stem cell and other primary cell cultures and can substantially reduce labor costs and reduce contamination risks associated with the scale-up of cellular therapies. The HPB will reduce costs and ease the translation of stem cell therapies from the research lab to the clinic.